Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging-related phenotypes in mice and macaques.

Abstract

Antler blastema progenitor cells (ABPCs) are a distinct population of skeletal mesenchymal stem cells found in regenerating deer antlers, with strong stemness and renewal capacity in vitro. Stem cell-derived extracellular vesicles (EVs) are emerging as potential therapeutic candidates that can mediate donor cells' beneficial effects. Here, we tested the effects of ABPC-derived EVs (EVs^ABPC) on aging in mice and rhesus macaques (Macaca mulatta). We identified a variety of unique factors in EVs^ABPC and showed that in vitro, EVs^ABPC attenuated phenotypes of senescence in bone marrow stem cells. In aged mice and macaques, EVs^ABPC substantially increased femoral bone mineral density. Further, intravenous EVs^ABPC improved physical performance, enhanced cognitive function and reduced systemic inflammation in aged mice, while reversing epigenetic age by over 3 months. In macaques, EV^ABPC treatment was also neuroprotective, reduced inflammation, improved locomotor function and reduced epigenetic age by over 2 years. Our findings position ABPCs as an emerging and practical source of EVs with translational value for healthy aging interventions.